The role of the arousal system in age‐related differences in cortical functional network architecture

Abstract

A common finding in the aging literature is that of the brain's decreased within‐ and increased between‐network functional connectivity. However, it remains unclear what is causing this shift in network organization with age. Given the essential role of the ascending arousal system (ARAS) in cortical activation and previous findings of disrupted ARAS functioning with age, it is possible that age differences in ARAS functioning contribute to disrupted cortical connectivity. We test this possibility here using resting state fMRI data from over 500 individuals across the lifespan from the Cambridge Center for Aging and Neuroscience (Cam‐CAN) population‐based cohort. Our results show that ARAS‐cortical connectivity declines with age and, consistent with our expectations, significantly mediates some age‐related differences in connectivity within and between association networks (specifically, within the default mode and between the default mode and salience networks). Additionally, connectivity between the ARAS and association networks predicted cognitive performance across several tasks over and above the effects of age and connectivity within the cortical networks themselves. These findings suggest that age differences in cortical connectivity may be driven, at least in part, by altered arousal signals from the brainstem and that ARAS–cortical connectivity relates to cognitive performance with age.

The role of ascending arousal network in patients with chronic insomnia disorder

“…The present study found that the ascending arousal nuclei were positively connected to each other within the AAN. These intranetwork results are consistent with those of recent studies on the FC of ascending arousal nuclei using resting‐state fMRI data (Beissner et al, 2014 ; Guardia et al, 2022 ; Singh et al, 2022 ). In addition, internetwork results showed increased positive FCs of AAN‐DMN, AAN‐CBN, and MRF‐PAG and increased negative FCs of AAN‐SMN and AAN‐DAN in patients with CID compared to GSCs.…”

“…The present study found that the ascending arousal nuclei were positively connected to each other within the AAN. These intranetwork results are consistent with those of recent studies on the FC of ascending arousal nuclei using resting-state fMRI data (Beissner et al, 2014;Guardia et al, 2022;Singh et al, 2022). In LC, MR, PBC, PO, and PPN were the major nodes that connected the AAN to other resting-state networks.…”

“…In recent years, using in vivo mapping of the human AAN, researchers have found that patients with acute and chronic disorders of consciousness (Snider et al, 2019 ; Snider et al, 2020 ) exhibit altered AAN connectivity. More recently, Guardia et al investigated the effect of age on the AAN and found that AAN‐cortical connectivity is significantly disrupted with age and that these connections could predict cognitive performance (Guardia et al, 2022 ). In our previous study, we found a disrupted LC (one nucleus of the AAN) FC network in patients with CID, and the alteration in FC connectivity was associated with symptoms of anxiety in patients (Gong, Shi, et al, 2021 ; Gong, Yu, et al, 2021 ).…”

Cognition’s dependence on functional network integrity with age is conditional on structural network integrity

“…We first demonstrated that function-structure connectivity convergence showed an age-related pattern similar to the pattern of resting-state functional connectivity established in previous literature: within network connections decrease and between network connections increase as age increases (Bethlehem et al, 2020;Betzel et al, 2014;L. Geerligs et al, 2014;Guardia et al, 2022). Overall function-structure connectivity convergence showed stronger correlations with multiple cognitive domains in comparison with functional connectivity observed and function-structure connectivity divergence.…”

“…We have proposed that the maintenance of cognitive function with advancing age is increasingly dependent on the integrity of functional brain networks (Tsvetanov et al, 2016). This proposal replicates across cognitive states (Tomassini et al, 2022;Tsvetanov et al, 2018), neuroimaging modalities (Tibon et al, 2021), analytical approaches (Bethlehem et al, 2020;Linda Geerligs & Tsvetanov, 2017;Guardia et al, 2022) and in individuals with genetically increased risk of dementia (Chan et al, 2021;Passamonti et al, 2019;Rittman et al, 2019;Tsvetanov, Gazzina, et al, 2021). However, the increased reliance on functional integrity for maintaining cognitive functions in later life is poorly understood.…”